rs746884948

Variant names:

• chr19-55185576-C-A
• rs746884948
• NM_002842.5:c.2988G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-55185576-C-A
• chr19-55185576-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002842.5(PTPRH):​c.2988G>T​(p.Leu996Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PTPRH NM_002842.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.264

Genes affected

PTPRH (HGNC:9672): (protein tyrosine phosphatase receptor type H) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP possesses an extracellular region, a single transmembrane region, and a single intracytoplasmic catalytic domain, and thus represents a receptor-type PTP. The extracellular region contains eight fibronectin type III-like repeats and multiple N-glycosylation sites. The gene was shown to be expressed primarily in brain and liver, and at a lower level in heart and stomach. It was also found to be expressed in several cancer cell lines, but not in the corresponding normal tissues. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRH	NM_002842.5	c.2988G>T	p.Leu996Phe	missense_variant	Exon 18 of 20	ENST00000376350.8	NP_002833.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRH	ENST00000376350.8	c.2988G>T	p.Leu996Phe	missense_variant	Exon 18 of 20	1	NM_002842.5	ENSP00000365528.2
PTPRH	ENST00000263434.5	c.2454G>T	p.Leu818Phe	missense_variant	Exon 16 of 18	1		ENSP00000263434.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T;.
Eigen	Benign	-0.090
Eigen_PC	Benign	-0.070
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.58	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L;.
PhyloP100		0.26
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.4	D;D
REVEL	Benign	0.15
Sift	Uncertain	0.0090	D;D
Sift4G	Uncertain	0.016	D;D
Polyphen		0.90	P;.
Vest4		0.47
MutPred		0.73		Gain of catalytic residue at L996 (P = 0.1187);.;
MVP		0.095
MPC		0.37
ClinPred		0.97	D
GERP RS		3.0
Varity_R		0.093
gMVP		0.24
Mutation Taster		=71/29	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Other links and lift over

dbSNP: rs746884948; hg19: chr19-55696944;